The invention disclosed herein concerns a process of making 1-Beta methyl carbapenems. 1-Betamethyl carbapenem antibiotics, particularly are well known for treating a broad spectrum of gram-negative and gram-positive bacterial infections. See for example U.S. Pat. No. 4,962,103 issued Oct. 9, 1990; U.S. Pat. No. 4,933,333 issued Jun. 12, 1990; U.S. Pat. No. 4,943,569 issued Jul. 24, 1990; U.S. Pat. No. 5,122,604 issued Jun. 16, 1992; U.S. Pat. No. 5,034,384 issued Jul. 23, 1991, ('256) and U.S. Pat. No. 5,011,832 issued Apr. 30, 1991.
Numerous routes to beta-methyl carbapenem intermediates of formula VI have been cited in the literature: ##STR2##
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Previous methods to stereoselectively prepare .beta.-methyl carbapenems include:
(1) hydrogenation of a 4-(2-propenyl) substituted azetidinone. PA0 (2) stereoselective protonation of an enolate ion. PA0 (3) reaction of 4-acetoxy azetidinone with a chiral enolate.
These methods required difficult multistep preparation of intermediates (1) and/or reagents (3), tedious manipulation of highly reactive intermediates at low temperature (2), or the use of expensive reagents (2,3).
The invention disclosed herein provides a versatile route to .beta.-methyl intermediates (VI Scheme 1 with high stereoselectivity from readily available starting materials in four steps.